Survival of T lymphocytes requires sustained Ca 2+ influx-dependent gene expression. The molecular mechanism, which governs sustained Ca 2+ influx in naive T lymphocytes, is unknown. Here we report an essential role for the β3 regulatory subunit of Ca v channels in the maintenance of naive CD8 + T cells. β3 deficiency resulted in a profound survival defect of CD8 + T cells. This defect correlated with depletion of the pore-forming subunit Ca v1.4 and attenuation of T cell receptor-mediated global Ca 2+ entry in the absence of β3 in CD8 + T cells. Ca v1.4 and β3 associated with T cell signaling machinery and Ca v1.4 localized in lipid rafts. Our data demonstrate a mechanism by which Ca 2+ entry is controlled by a Ca v1.4–β3 channel complex in T cells.